-
Biometals : An International Journal on... Jun 2016The observed biological differences in safety and efficacy of intravenous (IV) iron formulations are attributable to physicochemical differences. In addition to...
The observed biological differences in safety and efficacy of intravenous (IV) iron formulations are attributable to physicochemical differences. In addition to differences in carbohydrate shell, polarographic signatures due to ferric iron [Fe(III)] and ferrous iron [Fe(II)] differ among IV iron formulations. Intravenous iron contains Fe(II) and releases labile iron in the circulation. Fe(II) generates toxic free radicals and reactive oxygen species and binds to bacterial siderophores and other in vivo sequestering agents. To evaluate whether differences in Fe(II) content may account for some observed biological differences between IV iron formulations, samples from multiple lots of various IV iron formulations were dissolved in 12 M concentrated HCl to dissociate and release all iron and then diluted with water to achieve 0.1 M HCl concentration. Fe(II) was then directly measured using ferrozine reagent and ultraviolet spectroscopy at 562 nm. Total iron content was measured by adding an excess of ascorbic acid to reduce Fe(III) to Fe(II), and Fe(II) was then measured by ferrozine assay. The Fe(II) concentration as a proportion of total iron content [Fe(III) + Fe(II)] in different lots of IV iron formulations was as follows: iron gluconate, 1.4 and 1.8 %; ferumoxytol, 0.26 %; ferric carboxymaltose, 1.4 %; iron dextran, 0.8 %; and iron sucrose, 10.2, 15.5, and 11.0 % (average, 12.2 %). The average Fe(II) content in iron sucrose was, therefore, ≥7.5-fold higher than in the other IV iron formulations. Further studies are needed to investigate the relationship between Fe(II) content and increased risk of oxidative stress and infections with iron sucrose.
Topics: Administration, Intravenous; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Ferrous Compounds; Glucaric Acid; Iron-Dextran Complex; Maltose
PubMed: 26956439
DOI: 10.1007/s10534-016-9923-7 -
European Heart Journal Mar 2015
Topics: Cardiotonic Agents; Female; Ferric Compounds; Heart Failure; Humans; Iron Deficiencies; Male; Maltose
PubMed: 25336211
DOI: 10.1093/eurheartj/ehu392 -
European Journal of Heart Failure Jul 2013
Topics: Anemia, Iron-Deficiency; Erythrocyte Indices; Female; Ferric Compounds; Heart Failure; Hemoglobins; Humans; Male; Maltose
PubMed: 23794608
DOI: 10.1093/eurjhf/hft096 -
Journal of Bacteriology May 1981malB(+)malQ strains accumulate maltose via the maltose-binding-protein-dependent transport system but are unable to metabolize it. Nevertheless, some of the maltose is...
malB(+)malQ strains accumulate maltose via the maltose-binding-protein-dependent transport system but are unable to metabolize it. Nevertheless, some of the maltose is modified after entering the cell. This newly formed compound exhibited a higher R(f) value than did maltose upon thin-layer and paper chromatography with the usual sugar-separating solvents. Treatment of this compound with acid and alkali reformed maltose. The identity of this compound with acetylmaltose was derived from mass spectrometry. Nuclear magnetic resonance spectra of the compound confirmed the presence of the acetyl group but did not allow its precise location on the maltose moiety. However, linkage to the 1-position of maltose could be excluded. Analysis of the mass spectra indicated that the nonreducing end of maltose was acetylated. Other substrates of the maltose transport system, such as maltotetraose, maltopentaose, and maltohexaose, were also modified after accumulation into the cell. Several products were formed; the heterogeneity of these products was probably caused by different degrees of acetylation. The enzymatic activity responsible for maltose and maltodextrin acetylation is unknown. However, it is clear that the lacA-dependent thiogalactoside transacetylase was not necessary for the acetylation of maltose. Strains that accumulate maltose via a bypass of the normal malB-dependent transport system also acetylated maltose even in the absence of any malB gene products. Thus, the acetylating activity was not connected to the malB system. Acetylmaltose as well as acetylated maltodextrins was excreted into the medium. Acetylmaltose is not a substrate of the maltose transport system. Thus, maltose acetylation may be an effective detoxification mechanism.
Topics: ATP-Binding Cassette Transporters; Acetylation; Biological Transport; Carrier Proteins; Chemical Phenomena; Chemistry; Dextrins; Escherichia coli; Escherichia coli Proteins; Maltose; Maltose-Binding Proteins; Monosaccharide Transport Proteins; Polysaccharides
PubMed: 7012137
DOI: 10.1128/jb.146.2.725-732.1981 -
Drug Design, Development and Therapy Jan 2011High doses of intravenous iron have a role in the treatment of a number of clinical situations associated with iron deficiency, iron deficiency anemia, and blood loss.... (Review)
Review
High doses of intravenous iron have a role in the treatment of a number of clinical situations associated with iron deficiency, iron deficiency anemia, and blood loss. In the presence of functioning erythropoiesis, iron supplementation alone may be adequate to replenish iron stores and restore blood loss. Where hormone replacement with an erythropoiesis-stimulating agent is required, iron adequacy will optimize treatment. Intravenous iron offers a rapid means of iron repletion and is superior to oral iron in many circumstances, especially in the presence of anemia of chronic disease, where it appears to overcome the block to absorption of iron from the gastrointestinal tract and immobilization of stored iron. The clinical situations where high doses of iron are commonly required are reviewed. These include nondialysis-dependent chronic kidney disease, inflammatory bowel disease, obstetrics, menorrhagia, and anemia associated with cancer and its treatment. The literature indicates that high doses of iron are required, with levels of 1500 mg in nondialysis-dependent chronic kidney disease and up to 3600 mg in inflammatory bowel disease. New formulations of intravenous iron have recently been introduced that allow clinicians to administer high doses of iron in a single administration. Ferumoxytol is available in the US, has a maximum dose of 510 mg iron in a single administration, but is limited to use in chronic kidney disease. Ferric carboxymaltose can be rapidly administered in doses of 15 mg/kg body weight, up to a ceiling dose of 1000 mg. A test dose is not required, and it can be used more widely across a spectrum of iron deficiency and iron deficiency anemia indications. The latest introduction is iron isomaltoside 1000. Again, a test dose is not required, and it can be delivered rapidly as an infusion (in an hour), allowing even higher doses of iron to be administered in a single infusion, ie, 20 mg/kg body weight with no ceiling. This will allow clinicians to achieve high-dose repletion more frequently as a single administration. Treatment options for iron repletion have taken a major leap forward in the past two years, especially to meet the demand for high doses given as a single administration.
Topics: Anemia, Iron-Deficiency; Animals; Disaccharides; Dose-Response Relationship, Drug; Drug Administration Schedule; Ferric Compounds; Hemorrhage; Humans; Infusions, Intravenous; Iron; Iron Deficiencies; Maltose
PubMed: 21340038
DOI: 10.2147/DDDT.S15817 -
Indian Heart Journal 2017Iron administration especially intravenous iron therapy is associated with improvements in exercise capacity and quality of life in patients with chronic heart failure... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Iron administration especially intravenous iron therapy is associated with improvements in exercise capacity and quality of life in patients with chronic heart failure (CHF). Our aim was to assess effect of ferric carboxymaltose (FCM) on hospitalization and mortality outcomes in CHF.
MATERIALS AND METHODS
A literature search across PUBMED, Google Scholar and trials database www.clinicaltrials.gov was conducted to search for randomized controlled trials (till August 2016) comparing FCM to placebo in CHF with or without anaemia. Published human studies in English language which reported data on mortality and hospitalization rates were included. Primary outcome was rates of HF hospitalizations and secondary outcomes were hospitalization due to any cardiovascular (CV) cause, death due to worsening HF and any CV death.
RESULTS
From 17 studies identified, two were included in final analysis (n=760; 455 in FCM and 305 in placebo arms). We observed significantly lower rates of hospitalization for worsening HF in FCM arm [Risk Ratio (RR) 0.34, 95% confidence interval (CI) 0.19, 0.59, p=0.0001] as well as for any CV hospitalizations [RR 0.49, 95% CI 0.35, 0.70; p<0.0001] (figure). No heterogeneity in studies was seen for these two outcomes (I=0%, p>0.05). No significant treatment effect with FCM was noted in mortality from worsening HF (RR 0.41, 95% CI 0.02, 7.36; p=0.55) or any CV death (RR 0.80, 95% CI 0.40, 1.57; p=0.51).
CONCLUSION
FCM reduces hospitalization rates in CHF but may not reduce mortality outcome. This finding needs further evaluation in a large, prospective, randomized controlled trial.
Topics: Anemia, Iron-Deficiency; Ferric Compounds; Global Health; Heart Failure; Hospitalization; Humans; Infusions, Intravenous; Maltose; Prospective Studies; Quality of Life
PubMed: 29174251
DOI: 10.1016/j.ihj.2017.10.009 -
Biochemistry May 2018MalG511 is a genetically selected binding-protein-independent mutant of the Escherichia coli maltose transporter MalFGK, which retains specificity for maltose and shows...
MalG511 is a genetically selected binding-protein-independent mutant of the Escherichia coli maltose transporter MalFGK, which retains specificity for maltose and shows a high basal ATPase activity in the absence of maltose binding protein (MBP). It shows an intriguing biphasic behavior in maltose transport assays in the presence of MBP, with low levels of MBP stimulating the activity and higher levels (>50 μM) inhibiting the transport activity. Remarkably, the rescuing effect of the MBP suppressor mutant, MBPG13D, turns it into an attractive model for studying regulatory mechanisms in the ABC transporter superfamily. It is hypothesized that the special characteristics of MalG511 result from mutations that shift its equilibrium toward the transition state of MalFGK. We tested this hypothesis by using site-directed spin labeling in combination with electron paramagnetic resonance spectroscopy, which showed conformational changes in MalG511 and its interaction with MBP and MBPG13D during its catalytic cycle. We found that MalG511 utilizes the same alternate access mechanism as MalFGK, including all three open, semi-open, and closed states of the MalK dimer, to transport maltose across the membrane. However, the equilibrium of this mutant is shifted toward the semi-open state in its resting state and interacts with MBP with high affinity, providing an explanation for the inhibition of MalG511 by MBP at higher concentrations. In contrast, the mutant binding protein, MBPG13D, interacts with lower affinity and could restore MalG511 to a normal catalytic cycle.
Topics: ATP-Binding Cassette Transporters; Escherichia coli; Escherichia coli Proteins; Hydrolysis; Ligands; Maltose; Maltose-Binding Proteins; Mutagenesis, Site-Directed; Mutant Proteins; Protein Conformation; Protein Structure, Secondary; Spin Labels
PubMed: 29637782
DOI: 10.1021/acs.biochem.8b00266 -
Journal of Bacteriology Jun 2006Bacillus subtilis can utilize maltose and maltodextrins that are derived from polysaccharides, like starch or glycogen. In this work, we show that maltose is taken up by...
Bacillus subtilis can utilize maltose and maltodextrins that are derived from polysaccharides, like starch or glycogen. In this work, we show that maltose is taken up by a member of the phosphoenolpyruvate-dependent phosphotransferase system and maltodextrins are taken up by a maltodextrin-specific ABC transporter. Uptake of maltose by the phosphoenolpyruvate-dependent phosphotransferase system is mediated by maltose-specific enzyme IICB (MalP; synonym, GlvC), with an apparent K(m) of 5 microM and a V(max) of 91 nmol . min(-1) . (10(10) CFU)(-1). The maltodextrin-specific ABC transporter is composed of the maltodextrin binding protein MdxE (formerly YvdG), with affinities in the low micromolar range for maltodextrins, and the membrane-spanning components MdxF and MdxG (formerly YvdH and YvdI, respectively), as well as the energizing ATPase MsmX. Maltotriose transport occurs with an apparent K(m) of 1.4 microM and a V(max) of 4.7 nmol . min(-1) . (10(10) CFU)(-1).
Topics: Bacillus subtilis; Biological Transport; Genotype; Kinetics; Maltose; Operon; Phosphoenolpyruvate Sugar Phosphotransferase System; Plasmids; Polysaccharides; Restriction Mapping
PubMed: 16707683
DOI: 10.1128/JB.00213-06 -
Journal of Microbiology and... Aug 2022Trehalose is a non-conventional sugar with potent applications in the food, healthcare and biopharma industries. In this study, trehalose was synthesized from maltose...
Trehalose is a non-conventional sugar with potent applications in the food, healthcare and biopharma industries. In this study, trehalose was synthesized from maltose using whole-cell TBRC 1196 producing trehalose synthase (TreS) as the biocatalyst. The reaction condition was optimized using 1% Triton X-100 permeabilized cells. According to our central composite design (CCD) experiment, the optimal process was achieved at 35°C and pH 8.0 for 24 h, resulting in the maximum trehalose yield of 51.60 g/g after 12 h using an initial cell loading of 94 g/l. Scale-up production in a lab-scale bioreactor led to the final trehalose concentration of 51.91 g/l with a yield of 51.60 g/g and productivity of 4.37 g/l/h together with 8.24 g/l glucose as a byproduct. A one-pot process integrating trehalose production and byproduct bioremoval showed 53.35% trehalose yield from 107.4 g/l after 15 h by permeabilized cells. The residual maltose and glucose were subsequently removed by TBRC 12153, resulting in trehalose recovery of 99.23% with 24.85 g/l ethanol obtained as a co-product. The present work provides an integrated alternative process for trehalose production from maltose syrup in bio-industry.
Topics: Biocatalysis; Glucosyltransferases; Maltose; Metabolic Engineering; Pseudomonas; Trehalose
PubMed: 35791071
DOI: 10.4014/jmb.2202.02028 -
Revista Espanola de Enfermedades... Jun 2022Carboxymaltose iron (Ferinject®) is a formulation for intravenous (iv) administration, used for the treatment of iron deficiency anemia and/or iron deficiency when oral...
Carboxymaltose iron (Ferinject®) is a formulation for intravenous (iv) administration, used for the treatment of iron deficiency anemia and/or iron deficiency when oral administration of iron is not effective or due to intolerance. Its safety profile is excellent with few, but not nonexistent, side effects. Hypophosphatemia has been described as one of them. It is usually mild, transient and asymptomatic. However, in some cases it may be accompanied by nausea, asthenia, in addition to muscular and neurological symptoms and hematological alterations. It is, therefore, a potentially serious adverse effect whose prevalence is unknown and which requires high clinical suspicion to be detected.
Topics: Ferric Compounds; Humans; Hypophosphatemia; Iron; Maltose; Osteomalacia
PubMed: 35105150
DOI: 10.17235/reed.2022.8621/2022